Sections

Presentation

History

Nearly all cases of capillary malformation can be diagnosed by taking a careful history and performing a physical examination.

Onset

Capillary malformations are always present at birth, but they may not be apparent early in life because of neonatal anemia or plethora.

Location

Of capillary malformations, most involve the head and the neck. Of facial capillary malformations, 45% are more or less restricted to 1 of the 3 areas supplied by the divisions of the fifth cranial nerve (CN). Of facial capillary malformations, 55% involve an area innervated by more than 1 division of the fifth CN, crossing the midline or occurring bilaterally.

Growth

Growth of the capillary malformation is commensurate with that of the child. Capillary malformations remain present for life. Capillary malformations show no tendency toward involution.

Evolution

Capillary malformations may change from pink in infancy to red in early adulthood to deep purple during middle age in some individuals. The surface may become thickened with a cobblestonelike contour. Approximately 65% of facial capillary malformations develop these changes during adulthood.^[19]

Nodular vascular lesions may develop, usually in adulthood. Pyogenic granulomas (lobular capillary hemangiomas) with bleeding may develop in capillary malformations, even in childhood.^[18]

Associations

Capillary malformation may coexist with other vascular malformations. Geographic (ie, well-circumscribed, sharply bordered) cutaneous lesions carry a much higher probability of associated lymphatic malformations than blotchy stains, especially in patients with Klippel-Trenaunay syndrome.^[20]

Physical Examination

Early in life, the lesions appear as flat (macular), mostly well-circumscribed patches. The color varies from pink to red to purple. The color of the capillary malformation does not correlate with the capillary depth or diameter. Blanching with external pressure is variable. In infancy and childhood, the color darkens with crying, fever, or overheating. Capillary malformations are usually unilateral with fairly sharp midline cutoffs. The face is the most frequently affected site, followed by the upper part of the trunk.

Later in life, as the vasculature dilates, the capillary malformation may evolve into a raised, thickened plaque. The capillary malformation becomes deep-red to purple. Lesions may become studded with vascular papules, imparting a cobblestonelike appearance. Vascular papules often form and may be prone to bleeding. Skin and underlying soft tissue or bony hypertrophy may be present. Lobulated capillary hemangiomas (pyogenic granulomas) may form, especially with intraoral lesions.

Associated findings

Ocular and/or CNS involvement occurs in 9.5% of patients with facial capillary malformations. Involvement of V1 distribution seems to be a requirement. The highest incidence appears to be in patients in whom the capillary malformation involves the entire cutaneous distribution of V1, with 78% developing eye or CNS complications.^[21]

Glaucoma occurs in approximately 10% of patients with facial capillary malformations, and no leptomeningeal involvement is present. Glaucoma affects 27-45% of patients when capillary malformations involve the skin supplied by both the ophthalmic (CN V1) and the maxillary (CN V2) divisions of the fifth CN, the trigeminal nerve. Glaucoma is less frequent when the face is involved in only 1 of these upper divisions of the trigeminal nerve or if it is affected solely below the eye; however, the prevalence is increased with eyelid involvement. The prevalence may not be correlated with increased vascularity of the choroid or the bulbar conjunctiva. Glaucoma may be due to increased episcleral venous pressure with resultant elevated intraocular pressure, and it can occur without leptomeningeal involvement (eg, in the absence of Sturge-Weber syndrome).

Although difficult to treat, glaucoma associated with periorbital capillary malformations can occur early in childhood; thus, early referral for high-risk patients is important.

Other types of vascular malformations (venous, lymphatic, arterial, or mixed) may be present.

Associated syndromes

Capillary malformation is a cutaneous finding of several syndromes.

Sturge-Weber syndrome

Sturge-Weber syndrome (encephalofacial or encephalotrigeminal angiomatosis) is characterized by the triad of capillary malformations involving the upper facial dermis, the ipsilateral leptomeninges, and the ipsilateral cerebral cortex. It is caused by a somatic activating mutation in the GNAQ gene.^[22]Some authorities believe that only 2 features are necessary to make this diagnosis. The facial skin supplied by the ophthalmic branch (CN V1) of the trigeminal nerve must be involved with the capillary malformation for a patient to meet one of the criteria for Sturge-Weber syndrome.

Sturge-Weber syndrome occurs in less than 10% of patients with capillary malformations on the upper eyelid or the forehead. Involvement of areas on the face supplied by only CN V2 or CN V3 does not carry an increased risk for Sturge-Weber syndrome.

No relationship is apparent between the size of the facial capillary malformation and the severity of CNS involvement, and a small percentage of Sturge-Weber syndrome patients lack any cutaneous involvement.^[23]

Typically, capillary malformations associated with Sturge-Weber syndrome are more extensive than isolated capillary malformations, and patients often have bilateral facial involvement. Complications include glaucoma, seizures, hemiplegia, mental retardation, cerebral calcifications, subdural hemorrhage, and an increased prevalence of underlying soft tissue hypertrophy. Large variability exists in the severity of associated symptoms.

Klippel-Trenaunay syndrome

Klippel-Trenaunay syndrome (KTS) (angio-osteohypertrophy syndrome) manifests as a triad of capillary malformation, congenital varicose veins, and hypertrophy of underlying tissues, particularly skeletal overgrowth. The sex distribution is equal. The lower limbs are involved in 95% of patients, and involvement is unilateral in 85%. Most patients are asymptomatic at birth, but many experience problems later in childhood. Complications include varicose veins with venous thrombosis and pulmonary embolism; bleeding from varices, the rectum, or the bladder; skin ulceration; increased sweating overlying the capillary malformation; leg circumference or length discrepancy with resultant scoliosis; edema; and recurrent infections.^[24]Ultrasonographic measurement of the thigh arterial blood flow may be helpful in predicting future leg length discrepancies in patients with lower extremity capillary malformations.^[25]

Parkes-Weber syndrome

With Parkes-Weber syndrome, the diagnostic criteria include an AVM in addition to those listed above for Klippel-Trenaunay syndrome. AVFs are usually diffuse and difficult to ablate. Almost all patients present in childhood with an enlarged, warm extremity. The prognosis is worse than that associated with Klippel-Trenaunay syndrome. A positive bradycardic reaction (Nicoladoni-Branham sign) portends a poorer prognosis. This test is performed by occluding the arterial inflow by compression with a blood pressure cuff. In a limb with a hemodynamically significant AVM, this maneuver leads to reflex bradycardia secondary to a sharp rise in blood pressure. Complications include ulceration and severe lymphedema.

Diffuse capillary malformation with overgrowth

This is a recently proposed designation, which describes patients with an extensive, diffuse, reticulate capillary malformation and variable, but proportionate, hypertrophy without any major complications.^[26]A reticulate capillary malformation is defined as networklike, blotchy, nonuniform in color, and without distinct borders. This is in contradistinction to the darker "geographic" stains observed in KTS. These patients do not fit the diagnostic criteria of the other disorders marked by capillary malformations and overgrowth such as KTS or Parkes-Weber syndrome. Patients still require periodic evaluation to monitor for leg length discrepancy. They exhibit normal neurologic development and proportionate overgrowth rather than progressive, disproportionate asymmetry.

Cobb syndrome

In Cobb syndrome (cutaneomeningospinal angiomatosis), a cutaneous vascular lesion in the skin overlying the spine, is associated with vascular malformations (venous or arteriovenous) in the subjacent spinal meninges. Possible complications result from neurologic damage caused by mass effect on the spinal cord or nerves, bone erosion, and subarachnoid hemorrhage.

Wyburn-Mason syndrome

Wyburn-Mason syndrome (unilateral retinocephalic syndrome), also known as Bonnet-Dechaume-Blanc syndrome, manifests as facial capillary malformations associated with unilateral AVM of the retina and the intracranial optic pathway. Physical findings include monocular amblyopia, mild proptosis, and dilatation of conjunctival vessels. Capillary malformations may occur anywhere on the ipsilateral face (not just the eyelids or periorbitally), and they may have associated facial hypertrophy or occasional involvement of the optic chiasm, the hypothalamus, the midbrain, and the basal ganglia, with associated mental retardation or neurologic signs and symptoms.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome

CM-AVM syndrome is an autosomal dominant disorder caused by mutations in RASA1. Multifocal, small, round-to-oval, pinkish-to-red cutaneous capillary malformations are seen in over 90% of individuals with RASA1 mutations and pinpoint red macules with pale halos are seen in about 20% of patients with clinically diagnosed CM-AVM syndrome.^[27]At least some of the capillary malformations may actually be cutaneous AVMs or overly subcutaneous AVMs. Hypotrichosis has been described within the capillary malformations, suggesting that hair follicle development may also be affected by the causative mutation.^[28]These cutaneous capillary malformations can accompany an internal or cutaneous AVM or arteriovenous fistula (AVF). Intracerebral AVMs or AVFs have been reported in about 7% of patients with CM-AVM syndrome and can be associated cerebral vascular accidents.

PIK3CA-related overgrowth spectrum (PROS)

Several other mosaic disorders, caused by somatic activating mutations in the gene for PIK3CA, present with capillary malformations, in addition to other vascular malformations. PIK3CA is in the PI3K-AKT signaling pathway responsible for cell cycle/apoptosis regulation, metabolism, and angiogenesis. Among the syndromes included in the PROS, the most clinically significant include hemihyperplasia-multiple lipomatosis syndrome (HHML), CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal syndrome), and megaloencephaly-capillary malformation (MCAP).^[29]MCAP, previously termed macrocephaly-cutis marmorata telangiectatica congenita, is a multisystemic disorder characterized by prenatal and postnatal overgrowth, somatic and cerebral asymmetry, megalencephaly with cortical brain abnormalities, specifically polymicrogyria, cardiac arrhythmias, thickened and doughy-feeling subcutaneous tissue, and syndactyly or polydactyly. It has been proposed that Klippel-Trenaunay syndrome may also result from mutations within this pathway as well, but confirmation is lacking.^{[30, 31]}

Microcephaly-capillary malformation (MIC-CAP)syndrome

MIC-CAP syndrome is an autosomal recessive congenital neurocutaneous disorder severely affecting the central nervous system. It is characterized by marked microcephaly, seizures, psychomotor disability, and multiple cutaneous capillary malformations. Affected individuals have variable dysmorphic facial features and hypoplastic distal phalanges.^[32]It is caused by mutations in the STAMBP gene, which encodes the deubiquitinating (DUB) isopeptidase, which plays a role in cell surface receptor‒mediated endocytosis and sorting.

Nevus vascularis mixtus

Nevus vascularis mixtus is the name given when a capillary malformation is paired with nevus anemicus, an example of didymosis or twin spotting.

Associated skeletal or neurologic anomalies

Capillary malformation overlying the lumbar spine may be a marker for an underlying primary skeletal or neurologic anomaly, such as spinal dysraphism, tethered spinal cord, lipomeningocele, or diastematomyelia. The prevalence of underlying defects is increased when multiple abnormalities are present in the lumbar skin. Skin markers include acrochordons (skin tags), an abnormal tuft of hair (fawn's tail), lipomas, an irregular (usually deviated) gluteal cleft, or a dermal sinus tract or sacral dimple that is large or superior to the gluteal fold.

Guggisberg et al found that none of 16 patients with an isolated capillary malformation showed occult spinal dysraphism, whereas 7 of 10 patients with capillary malformations in combination with other lumbar congenital anomalies did have an occult spinal dysraphism.^[33]Conversely, Tubbs et al found that 21 (17.5%) of 120 patients with an isolated capillary malformation harbored an occult spinal dysraphism, and they recommended MRI for all patients who present with an isolated lumbar capillary malformation.^[34] This approach is not widely accepted, however.

Associated dermatologic anomalies

Phakomatosis pigmentovascularis

Phakomatosis pigmentovascularis refers to the presence of a capillary malformation with a melanocytic or other type of nevus. The histopathologic findings of a capillary malformation in phakomatosis pigmentovascularis are the same as those for isolated capillary malformations.

Four types of phakomatosis pigmentovascularis are described, as follows:

Type I is composed of capillary malformation and nevus pigmentosus et verrucosus or epidermal nevus.
Type II is a capillary malformation and dermal melanocytosis with or without nevus anemicus; this is the most common type. It also includes nevus of Ota (oculocutaneous melanosis) and can be associated with Sturge-Weber syndrome and Klippel-Trenaunay syndrome.
Type III is a capillary malformation and nevus spilus with or without nevus anemicus.
Type IV is a capillary malformation, nevus spilus, and dermal melanocytosis with or without nevus anemicus.

Subdivisions of each type include subtype a for cutaneous involvement only and subtype b for cutaneous and systemic involvement. No systemic involvement is reported for type I.

In 2005, another classification scheme for phakomatosis pigmentovascularis has been proposed by Happle. This includes 3 different distinct categories based on the type of associated lesion: phacomatosis cesioflammea (capillary malformation with bluish gray spots as observed with various lesions of dermal melanocytosis), phacomatosis spilorosea (pale pink telangiectatic capillary malformation associated with a nevus spilus), and phacomatosis cesiomarmorata (cutis marmorata telangiectatica congenita with blue spots). A final category includes others that cannot be included in one of the other 3 variants.^[35]

Angiolipomas

Asymptomatic, noninfiltrating angiolipomas may be present underlying a capillary malformation in a small minority of patients. These are mostly found on the trunk and pelvic girdle skin and may be associated with laser-resistant capillary malformations.^[36]

Complications

Occasionally capillary malformations are complicated by an overlying eczematous dermatitis. The mechanism for this is unknown but has been compared with stasis dermatitis, given the dilated dermal capillaries in each condition. The dermatitis is responsive to topical steroids or topical calcineurin inhibitors; however, it readily recurs shortly after discontinuation of treatment. Laser ablation of the underlying capillary malformation can treat this dermatitis; however, some capillary malformations can develop dermatitis even after laser ablation of the stain.^[37]

Differential Diagnoses

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Media Gallery

Histopathologic features of a capillary malformation (nevus flammeus) showing telangiectatic vessels lined by mature-appearing endothelial cells.
Capillary malformation on the left preauricular aspect of the cheek, the ear, and the neck in a neonate (same patient as in Media Files 3-4).
Same patient as in Media Files 2 and 4 immediately after test spots with the pulsed-dye laser at 585 nm. Note the purpuric macules where the laser impacted in a linear distribution on the preauricular aspect of the cheek.
Same patient as in Media Files 2-3 after 4 treatments with the pulsed-dye laser. Treatments were given at 2-month intervals in an outpatient setting using topical anesthetic.